The IgM antibody response to the lipoteichoic acid (LTA) isolated from staphylococcus aureus ATCC 6538P was examined by a newly developed procedure in which erythrocytes, sensitized with periodate-activated LTA, were used for the detection of IgM-producing plaque-forming cells (PFC). LTA-specific PFC were first detected two days after immunization with heat-killed bacteria and maximal PFC were attained by day four; specificity of such PFC was affirmed by plaque-inhibition tests. No PFC were found in mice given isolated LTA over a 10,000-fold range of immunizing doses. Mice, pretreated with a carrier known to activate thymus-derived (T) helper lymphocytes, produced a PFC response to LTA only when immunized with LTA bound to the same carrier. This suggest that carrier-specific helper T cells are needed to initiate an antibody response to poorly-immunogenic LTA. Since an antibody response can be elicited in mice given heat-killed bacterial cells, bacterial cell wall and/or cell membrane components may play an important role as immunological carriers of this molecule.